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  • 1
    Online Resource
    Online Resource
    Cham :Springer International Publishing AG,
    Keywords: Neurosciences. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (475 pages)
    Edition: 1st ed.
    ISBN: 9783319588117
    Series Statement: Advances in Neurobiology Series ; v.17
    DDC: 612.8
    Language: English
    Note: Intro -- Foreword -- About the Editors -- Preface -- Contents -- Contributors -- Part I: PDEs and Signaling, Circuitry, and Implications of CNS Functions and Disorders -- Chapter 1: Phosphodiesterase Diversity and Signal Processing Within cAMP Signaling Networks -- 1.1 Introduction -- 1.2 The Range of Kinetic Characteristics of PDE Isoforms Fine-Tunes cAMP Levels -- 1.3 Regulation of PDEs Activities Expands Their Catalytic Capabilities to Allow Rapid Signal Modulation and Integration -- 1.4 The Diversity of PDE Subcellular Localizations Promotes Signal Specificity -- 1.5 Conclusions -- References -- Chapter 2: Current Understanding of PDE10A in the Modulation of Basal Ganglia Circuitry -- 2.1 Introduction -- 2.2 The Role of the Striatum as Part of the Basal Ganglia -- 2.2.1 Anatomy and Circuitry of the Basal Ganglia -- 2.2.2 Properties of Striatal Medium Spiny Neurons -- 2.3 Expression of Phosphodiesterases in the Basal Ganglia -- 2.3.1 Expression of the Striatal Enriched PDEs -- 2.3.2 Expression of PDE10A in MSNs of the Striatum -- 2.4 Role of PDE10A in Modulating Basal Ganglia Circuitry -- 2.4.1 Cellular Effects of PDE10A on Cyclic Nucleotide Signaling -- 2.4.2 Differential Effects of PDE10A Inhibition Between Striatonigral and Striatopallidal Neurons -- 2.4.3 Contribution of cGMP Signaling -- 2.5 The Physiological Role of PDE10A and Its Relevance in Basal Ganglia Diseases -- 2.5.1 The Role of PDE10A in Regulating Motor Function -- 2.5.2 PDE10A Inhibition to Treat Neurodegenerative Motor Disorders -- 2.5.3 Involvement of PDE10A in the Pathophysiology of Schizophrenia and Related Disorders -- 2.5.4 Involvement of PDE10A in the Reward System -- 2.6 Discussion -- References -- Chapter 3: Interaction of Cdk5 and cAMP/PKA Signaling in the Mediation of Neuropsychiatric and Neurodegenerative Diseases -- 3.1 A Brief Introduction. , 3.2 Cdk5 and Cdk5 Cofactors -- 3.3 Cdk5 Phosphorylates Multiple Substrates of the cAMP Signaling Pathway -- 3.3.1 PDE4 -- 3.3.2 DARPP-32 and PP1 -- 3.3.3 TH -- 3.3.4 Coronin 1 -- 3.3.5 Disrupted-in-Schizophrenia 1 (DISC1) -- 3.3.6 Synapsin III -- 3.4 Cdk5 Is Associated with Memory, Learning via the cAMP Signaling Pathway -- 3.5 Cdk5 Regulates PDE4 Signaling on Stress Exposure and Its Association with Anxiety and Depression -- 3.6 Reciprocal Regulation of Cdk5 and cAMP/PKA Signaling on Dopaminergic Signaling and Its Association with Parkinson's Disease -- 3.7 Interaction of Cdk5 and cAMP/PKA Pathway in Dopamine Signaling and Its Association with Drug Addiction -- 3.8 Role of Cdk5 and cAMP/PKA Signaling in Mediating Neuropsychiatric Disorders -- 3.9 Conclusions -- References -- Chapter 4: The PDE4 cAMP-Specific Phosphodiesterases: Targets for Drugs with Antidepressant and Memory-Enhancing Action -- 4.1 Introduction -- 4.2 The Structure of the PDE4 Genes and Their Transcripts -- 4.3 Dimerization of PDE4 Isoforms and Its Implication for Drug Discovery -- 4.4 Dimerization and the Phosphorylation of PDE4s -- 4.5 Dimerization and Interaction of PDE Isoforms with Their Protein "Partners" -- 4.6 PKA Substrates as Mediators of PDE4 Action in the CNS -- 4.6.1 CREB -- 4.6.2 Cytoplasmic PKA Targets: LKB1 and GSK-3β Kinases -- 4.6.3 Cytoplasmic PKA Targets: DARPP32 -- 4.6.4 Ion Channels -- 4.6.5 Synaptic Vesicle Proteins -- 4.6.6 Ubiquitin Ligases -- 4.7 Cellular Functions of PDE4 Action in the CNS -- 4.7.1 PDE4s and Neurogenesis -- 4.7.2 PDE4s, Neuronal Polarity and the Formation of Axons and Dendrites -- 4.7.3 PDE4s and Synaptic Function -- 4.8 Regional Expression of PDE4 Isoforms in the CNS and Potential Functional Implications. , 4.8.1 Regional Distribution of PDE4 Isoforms in Brain Regions Involved in Dopaminergic Signaling: Addictive Behaviors, Depression and Schizophrenia -- 4.9 CNS Effects of PDE4 Inhibitors -- 4.10 Studies of PDE4 Function in the CNS Using Genetically-Modified Mice -- 4.10.1 PDE4 Gene Knockouts -- 4.10.2 Lentiviral siRNA -- 4.10.3 Dominant-Negative PDE4 Mutants -- 4.10.4 What Have We Learned from the Mouse Models? -- 4.11 Human PDE4D Mutations: Acrodysostosis Syndromes -- 4.12 Dimerization and the PDE4D Acrodysostosis Mutations -- 4.13 Conclusion: Implications for Future PDE4 CNS Drug Development -- References -- Chapter 5: Phosphodiesterase-4B as a Therapeutic Target for Cognitive Impairment and Obesity-Related Metabolic Diseases -- 5.1 Introduction -- 5.2 Effects of Pan-PDE4 Inhibitors on Cognitive Impairment -- 5.2.1 Age-Associated Cognitive Decline -- 5.2.2 Alzheimer's Disease -- 5.2.3 Frontotemporal Dementia -- 5.2.4 Fragile X Syndrome -- 5.3 Metabolic Effects of PDE4 Inhibition -- 5.3.1 Obesity -- 5.3.2 Alcoholic Fatty Liver -- 5.3.3 Diabetes -- 5.4 Adverse Effects of PDE4 Inhibition -- 5.4.1 Role of PDE4D in Nausea and Emesis -- 5.4.2 Vascular Injury -- 5.5 Selective Inhibition of PDE4B -- 5.5.1 Specific Inhibition of PDE4B in Mice -- 5.5.2 PDE4B-Selective Inhibitors -- 5.5.3 Traumatic Brain Injury -- 5.6 Concluding Remarks -- Reference -- Part II: PDEs in Cognition of Aging and Alzheimer's Disease -- Chapter 6: From Age-Related Cognitive Decline to Alzheimer's Disease: A Translational Overview of the Potential Role for Phosphodiesterases -- 6.1 Age-Related Cognitive Decline, Alzheimer's Disease and Phosphodiesterases -- 6.1.1 Phosphodiesterases and Signal Transduction -- 6.1.2 Neuroplasticity -- 6.1.3 Neuroprotection -- 6.1.4 Blood Flow and Glucose Metabolism -- 6.2 Localization -- 6.3 Translational Data on Cognition Enhancement. , 6.3.1 Phosphodiesterase 1 Inhibition -- 6.3.2 Phosphodiesterase 2 Inhibition -- 6.3.3 Phosphodiesterase 3 Inhibition -- 6.3.4 Phosphodiesterase 4 Inhibition -- 6.3.5 Phosphodiesterase 5 Inhibition -- 6.3.6 Phosphodiesterase 6 Inhibition -- 6.3.7 Phosphodiesterase 7 Inhibition -- 6.3.8 Phosphodiesterase 8 Inhibition -- 6.3.9 Phosphodiesterase 9 Inhibition -- 6.3.10 Phosphodiesterase 10 Inhibition -- 6.3.11 Phosphodiesterase 11 inhibition -- 6.4 Discussion -- 6.4.1 Preclinical Conclusions -- 6.4.2 Clinical conclusions -- 6.4.3 Translational Aspects -- 6.4.4 Overall Conclusions -- References -- Chapter 7: The Past, Present, and Future of Phosphodiesterase-4 Modulation for Age-­Induced Memory Loss -- 7.1 Introduction and Background of PDE4 -- 7.1.1 PDE4A -- 7.1.2 PDE4B -- 7.1.3 PDE4D -- 7.2 Differences Between Normal Aging and Pathological Aging -- 7.3 Alterations of cAMP/PDE4 Signaling in Normal Aging -- 7.4 Alterations of cAMP/PDE4 Signaling in Pathological Aging -- 7.5 Evidence for PDE4 Modulation as a Therapeutic Target in Pathological and Non-Pathological Aging -- 7.6 Pitfalls and Side Effects of PDE4 Inhibition -- 7.7 The Future of PDE4 for Therapeutic Intervention -- References -- Chapter 8: A Role for Phosphodiesterase 11A (PDE11A) in the Formation of Social Memories and the Stabilization of Mood -- 8.1 Introduction -- 8.2 Molecular Features of PDE11A -- 8.3 Tissue Expression Patterns for PDE11A -- 8.4 A Role for PDE11A in Brain Function -- 8.5 PDE11A Pharmacological Tools -- 8.6 Future Considerations for PDE11A Research -- 8.7 Summary -- References -- Chapter 9: Role of PDE9 in Cognition -- 9.1 Introduction -- 9.2 Gene Organization, Splice Variants and Expression -- 9.3 Enzymology -- 9.3.1 PDE9 Enzymatic Profile and Crystal Structure -- 9.3.2 Selective PDE9 Inhibitors -- 9.4 Protein Expression and Function -- 9.4.1 Brain Expression. , 9.4.2 Cognition -- 9.4.2.1 The Second Messenger cGMP -- 9.4.2.2 PDE9 Inhibition and Synaptic Plasticity -- 9.4.2.3 Effects of PDE9 Inhibition on Cognition -- 9.4.3 Role of PDE9 in Other Physiological and Pathophysiological Conditions -- 9.4.3.1 Heart Failure -- 9.4.3.2 Sickle Cell Disease -- 9.4.3.3 Erectile Dysfunction -- 9.4.3.4 Retina -- 9.5 PDE9 and Its Relevance in Cognitive Disorders -- 9.5.1 Link to Alzheimer's Disease -- 9.5.2 Link to Huntigton -- 9.5.3 Link to Schizophrenia -- References -- Part III: PDEs in Parkinson's and Huntington's Diseases -- Chapter 10: Regulation of Striatal Neuron Activity by Cyclic Nucleotide Signaling and Phosphodiesterase Inhibition: Implications for the Treatment of Parkinson's Disease -- 10.1 Cyclic Nucleotide Synthesis -- 10.2 Impact of Striatal Dopamine Signaling on Striatal Neuronal Excitability -- 10.3 Role of Striatal NO-cGMP Signaling in the Modulation of Striatal Neuron Excitability -- 10.4 Phosphodiesterase Control of Striatal Neuronal Excitability -- 10.5 Phosphodiesterase Expression and Control of Striatal Striatonigral and Striatopallidal Projection Pathways -- 10.5.1 Dual-Substrate Phosphodiesterases -- 10.5.2 cAMP-Specific Phosphodiesterases -- 10.5.3 cGMP-Specific Phosphodiesterase -- 10.6 Cyclic Nucleotide Control of Striatal Synaptic Plasticity -- 10.7 Targeting Cyclic Nucleotide Phosphodiesterases for the Treatment of L-DOPA-Induced Dyskinesia in PD -- References -- Chapter 11: Role of Phosphodiesterases in Huntington's Disease -- 11.1 Introduction -- 11.2 Cyclic Nucleotides Phosphodiesterases -- 11.2.1 PDEs in the Brain -- 11.2.1.1 Regional Distribution of PDEs -- 11.2.2 Cellular and Subcellular PDEs Distribution -- 11.2.3 Functions of PDEs in Relation to their Distribution -- 11.3 Role of PDE in the PKA/CREB/BDNF Pathway -- 11.4 PDEs in Huntington's Disease. , 11.4.1 PDEs Inhibition Effects in Huntington Disease.
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  • 2
    Online Resource
    Online Resource
    Washington, DC :American Chemical Society,
    Keywords: Polymers-Effect of radiation on-Congresses. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (357 pages)
    Edition: 1st ed.
    ISBN: 9780841213838
    Series Statement: ACS Symposium Series ; v.No. 527
    DDC: 620.19204228
    Language: English
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  • 3
    Online Resource
    Online Resource
    Washington, DC :American Chemical Society,
    Keywords: Polymers-Effect of radiation on-Congresses. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (285 pages)
    Edition: 1st ed.
    ISBN: 9780841212336
    Series Statement: ACS Symposium Series ; v.No. 381
    DDC: 620.1/9204228
    Language: English
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  • 4
    Publication Date: 2020-08-13
    Description: The complexity of an ecological community can be distilled into a network, where diverse interactions connect species in a web of dependencies. Species interact directly with each other and indirectly through environmental effects, however to our knowledge the role of these ecosystem engineers has not been considered in ecological network models. Here we explore the dynamics of ecosystem assembly, where species colonization and extinction depends on the constraints imposed by trophic, service, and engineering dependencies. We show that our assembly model reproduces many key features of ecological systems, such as the role of generalists during assembly, realistic maximum trophic levels, and increased nestedness with mutualistic interactions. We find that ecosystem engineering has large and nonlinear effects on extinction rates. While small numbers of engineers reduce stability by increasing primary extinctions, larger numbers of engineers increase stability by reducing primary extinctions and extinction cascade magnitude. Our results suggest that ecological engineers may enhance community diversity while increasing persistence by facilitating colonization and limiting competitive exclusion.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
    Format: application/pdf
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  • 5
    Publication Date: 2022-05-26
    Description: © The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Estuaries and Coasts 39 (2016): 311-332, doi:10.1007/s12237-015-0011-y.
    Description: Numerical modeling has emerged over the last several decades as a widely accepted tool for investigations in environmental sciences. In estuarine research, hydrodynamic and ecological models have moved along parallel tracks with regard to complexity, refinement, computational power, and incorporation of uncertainty. Coupled hydrodynamic-ecological models have been used to assess ecosystem processes and interactions, simulate future scenarios, and evaluate remedial actions in response to eutrophication, habitat loss, and freshwater diversion. The need to couple hydrodynamic and ecological models to address research and management questions is clear because dynamic feedbacks between biotic and physical processes are critical interactions within ecosystems. In this review, we present historical and modern perspectives on estuarine hydrodynamic and ecological modeling, consider model limitations, and address aspects of model linkage, skill assessment, and complexity. We discuss the balance between spatial and temporal resolution and present examples using different spatiotemporal scales. Finally, we recommend future lines of inquiry, approaches to balance complexity and uncertainty, and model transparency and utility. It is idealistic to think we can pursue a “theory of everything” for estuarine models, but recent advances suggest that models for both scientific investigations and management applications will continue to improve in terms of realism, precision, and accuracy.
    Description: NKG, ALA, and RPS acknowledge support from the USGS Coastal and Marine Geology Program. DKR gratefully acknowledges support from NSF (OCE-1314642) and NIEHS (1P50-ES021923-01). MJB and JMPV gratefully acknowledge support from NOAA NOS NCCOS (NA05NOS4781201 and NA11NOS4780043). MJB and SJL gratefully acknowledge support from the Strategic Environmental Research and Development Program—Defense Coastal/Estuarine Research Program (RC-1413 and RC-2245).
    Keywords: Numerical modeling ; Hydrodynamics ; Ecological modeling ; Ecosystem modeling ; Skill assessment
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 66 (1996), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The present study examined the in vivo regulation of rolipram-sensitive, high-affinity cyclic AMP phosphodiesterase (PDE4) in rat cerebral cortex. The hydrolysis of cyclic AMP, formed by stimulation of β-adrenergic receptors, was measured in cerebral cortical slices. Hydrolysis of cyclic AMP formed under these conditions was inhibited by the PDE4-selective inhibitor rolipram but not by selective inhibitors of other PDE families. Intraventricular infusion of 6-hydroxydopamine (6-OHDA; 200 µg) decreased the rate constant of cyclic AMP hydrolysis and increased the cyclic AMP half-life 17 days, but not 1 or 7 days, following the treatment. A reduction in norepinephrine (NE) content occurred first; the NE level was reduced to 42, 24, and 6% of control at 1, 7, and 17 days after 6-OHDA infusion, respectively. This was followed by the development of supersensitivity of β-adrenergic receptor-linked adenylyl cyclase, which occurred 7 days after the infusion. The reduction in PDE4 activity occurred last. When a higher dose of 6-OHDA (300 µg) was used, the reduction in the rate constant of cyclic AMP hydrolysis occurred by 7 days; at this time NE content was depleted to 6% of control. Similar to 6-OHDA treatment, continuous blockade of β-adrenergic receptors, produced by chronic propranolol infusion, decreased the rate constant of cyclic AMP hydrolysis. Therefore, the current results indicate that diminished stimulation of β-adrenergic receptors, either by loss of noradrenergic innervation or by receptor blockade, reduces the activity of PDE4. This suggests that PDE4 regulation may contribute in the homeostasis of the noradrenergic receptor-effector system in the brain.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 74 (2000), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In a previous study, an up-regulation of rolipram-sensitive, low-Km, cyclic AMP phosphodiesterase (PDE4) subtype PDE4A in rat cerebral cortex following repeated treatment of desipramine was observed. To determine whether this effect is shared by antidepressants from different pharmacological classes, PDE4A expression was examined using immunoblot analyses following repeated treatment with the norepinephrine reuptake inhibitor desipramine, the monoamine oxidase inhibitor phenelzine, the atypical antidepressant trazodone, and the serotonin reuptake inhibitor fluoxetine. Desipramine, phenelzine, and fluoxetine all increased the intensities of the PDE4A bands in hippocampal preparations; trazodone did not. In preparations of cerebral cortex, the intensities of the PDE4A bands were increased following desipramine treatment, not changed following phenelzine or fluoxetine treatment, and decreased following trazodone treatment. It appears that repeated treatment with antidepressant drugs from different pharmacological classes produces similar effects on the expressions of PDE4A variants in hippocampus. This effect is not correlated with the changes in β-adrenergic receptor densities, suggesting these antidepressants may at some point alter intracellular signal transduction pathways in a similar manner.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: In a previous study, it was observed that the activity of rolipram-sensitive, low-Km, cyclic AMP phosphodiesterase (PDE4) was decreased in vivo with diminished noradrenergic stimulation. The results of the present experiments indicated that the reduction in the activity may be associated with down-regulation of PDE4 protein. Immunoblot analysis using PDE4-specific, subfamily-nonspecific antibody (K116) revealed four major bands of PDE4 in rat cerebral cortex; those with apparent molecular masses of 109 and 102 kDa are variants of PDE4A. Diminished noradrenergic activity, produced by intracerebroventricular infusion of 6-hydroxydopamine (6-OHDA) or chronic subcutaneous infusion of propranolol, decreased the intensities of the protein bands for the 109- and 102-kDa PDE4A variants in rat cerebral cortex but not of the 98- or 91-kDa PDE4 forms. 6-OHDA-induced noradrenergic lesioning also decreased the content of 102-kDa PDE4A in hippocampus as labeled by PDE4A-specific antibody (C-PDE4A). Enhanced noradrenergic stimulation up-regulated PDE4 in cerebral cortex. This was indicated by the finding that repeated treatment with desipramine increased the intensity of the protein band for the 102-kDa PDE4 but not for the other variants of PDE4. These results suggest that PDE4 subtypes are differentially regulated at the level of expression, as evidenced by an apparent change in the amount of PDE4 protein, following changes in noradrenergic activity. These observations are consistent with the notion that PDE4s, especially the PDE4A variants with molecular masses of 109 and 102 kDa, play an important role in maintaining the homeostasis of the noradrenergic signal transduction system in the brain and may be involved in the mediation of antidepressant activity.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of the American Chemical Society 77 (1955), S. 5655-5657 
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1520-5835
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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